Novel and Highly Efficient Synthesis of Substituted Dibenz[b,g]1,5-oxazocines. A Direct Comparison of the Solution versus Solid-Phase Approach

We describe a novel and highly efficient synthesis of substituted dibenz[b,g]1,5-oxazocines. The procedure is based on the SNAr of fluoride with the phenolic hydroxide of the properly assembled acyclic intermediate. A direct comparison of the solution-phase vs the solid-phase synthesis has been conducted. The speed of the synthesis, the purity of the desired eight-membered heterocycles (>95%), as well as the diversity of the resultant library are definite advantages of the solid-phase procedure. Yields of dibenz[b,g]1,5-oxazocines synthesized via the solid-phase approach were generally better, while the purity of the products synthesized by both methods were identical.